The ubiquitin ligase Phr1 regulates axon outgrowth through modulation of microtubule dynamics (Neuron, 2007, 56:604-620)

報告日期: 2008/05/23
報告時間: 15:10/16:00
報告學生: 王仁伶
講評老師: 李宜釗

The Ubiquitin Ligase Phr1 Regulates Axon Outgrowth through Modulation of Microtubule Dynamics


Neuron (2007) 56: 604–620


Speaker: Jen-Ling Wang (王仁伶)             

Commentator: Dr. Yi-Chao Lee (李宜釗老師)           

Date: 5/ 23/ 08 17:10-18:00

Place: Room 602


Neuronal connections are achieved by nascent axons navigating to the appropriate postsynaptic targets. Many studies have shown that a lot of molecules are involved in axon pathfinding; however, our understanding of this complex developmental process is still fragmentary. To understand the molecular and temporal regulation of these developmental steps more comprehensive, the authors used forward genetic screen for recessive alleles affecting motor axon navigation in GFP reportor mice mutagenized with ENU. In Magellan mutants, motor and sensory neurons displayed more sever projection errors, axon growth and pathfinding defects, but normal response to guidance cues. They mapped the Magellan mutation to the Phr1 gene encoding a large multidomain E3-ubiquitin ligase. Phr1 is associated with the microtubule cytoskeleton and is enriched in axon shafts but not in their growth cones. In Magellan mutant axons (Phr1-/-) do not maintain the proper cytoskeleton polarization, which results in an excess of microtubules in the growth cone and F-actin-rich patches along the axon shaft. Inhibition of P38MAPK by SB203580 or enhancement of microtubule stabilization by taxol restored normal microtubules in the growth cones of Magellan mutants. Taken together, Phr1 are coordinated the cytoskeletal organization that distinguishes axons from growth cones to achieve efficacious axon pathfinding.